Diarrhea (diarrhoea)

Diarrhea is the passage of 3 or more loose or liquid stools per day, or more frequently than is normal for the individual. It is usually a symptom of gastrointestinal infection, which can be caused by a variety of bacterial, viral and parasitic organisms. Infection is spread through contaminated food or drinking-water, or from person to person as a result of poor hygiene.
Severe diarrhea leads to fluid loss, and may be life-threatening, particularly in young children and people who are malnourished or have impaired immunity.

Diarrhea can usually be divided into different types and treatment will vary depending on cause: secretory, osmotic, mechanical, or disordered motility.
In palliative care, the overuse of laxatives, typically seen when the management of constipation is suddenly "stepped-up", is a common cause. Other causes include partial intestinal obstruction, pancreatic insufficiency, Clostridium difficile infection, chemotherapeutics, and radiation enteritis.
Severe constipation and fecal impaction can also cause diarrhea as backed-up, liquefied stool may be all that the patient can pass (‘overflow diarrhea").

Treatment

General: ensure adequate hydration.

Medications:
- Kaolin and pectin is a suspension of adsorbent and bulk-forming agents, which can provide modest relief from diarrhea - it may take up to 48 hours to produce an effect and can interfere with the absorption of certain medications.
- Antibiotics: infectious diarrhea should be identified and treated with appropriate antibiotics, particularly C. difficile enteritis.
- Bismuth has an additional antimicrobial effect, and can be added for increased symptomatic control against organisms such as enterotoxigenic E. Coli.
- Loperamide, an opioid, reduces peristalsis in the gut, increases water reabsorption, and promotes fecal continence, making it a potent anti-diarrheal agent. The initial dose is 4 mg, with titration to 2 mg after each loose stool, with the typical dose being 4 – 8 mg per day.
- Aspirin and cholestyramine can reduce the diarrhea in radiation-induced enteritis, as can addition of a stool bulking agent such as psyllium.
- Mesalamine and other anti inflammatories are used for inflammatory bowel disease.
- Pancreatic enzymes such as pancrelipase are used for pancreatic insufficiency.
- Octreotide is effective with profuse secretory diarrhea seen in HIV disease, and those with high effluent volume from a stoma.

Definition
 Diarrhoea is defined by WHO as having three or more loose or liquid stools per day, or as having more stools than is normal for that person.
 It is usually a symptom of gastrointestinal infection, which can be caused by a variety of bacterial, viral and parasitic organisms. Infection is spread through contaminated food or drinking-water, or from person to person as a result of poor hygiene.
 Severe diarrhoea leads to fluid loss, and may be life-threatening, particularly in young children and people who are malnourished or have impaired immunity.
 Diarrhoea can usually be divided into different types and treatment will vary depending on cause: secretory, osmotic, mechanical, or disordered motility.
 In palliative care, the overuse of laxatives, typically seen when the management of constipation is suddenly "stepped-up", is a common cause. Other causes include
partial intestinal obstruction, pancreatic insufficiency, Clostridium difficile infection, chemotherapeutics, and radiation enteritis.
 Severe constipation and faecal impaction can also cause diarrhoea as backed-up, liquefied stool may be all that the patient can pass (“overflow diarrhoea").

Scope
 Management of diarrhoea comprises identification and, if appropriate, treatment of possible underlying cause(s)
 Adequate hydration needs to be part of the treatment for diarrhoea, including the use of rehydration salts. This application only covers pharmacological treatment.

Loperamide in the treatment of diarrhoea
 It is a synthetic piperidine derivative is an opioid drug effective against diarrhoea resulting from gastroenteritis or inflammatory bowel disease.
 It reduces peristalsis in the gut, increases water reabsorption, and promotes faecal continence.
 It is an opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the large intestine; by itself it does not affect the central nervous
system.
 It works by decreasing the activity of the myenteric plexus, which, like morphine, decreases the tone of the longitudinal smooth muscles but increases the tone of circular smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the faecal matter. Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex.
 It may be less effective in patients with extensive colorectal resections. In these patients octreotide may be more effective.

Additional supporting information for this drug:
 In most countries of the world loperamide is available generically. The oral application is easier that the subcutaneous injection required for octreotide therapy.
 AIDS-related diarrhoea is a common cause of morbidity and mortality in HIV positive individuals, especially in the sub-Saharan Africa. Loperamide is readily available and has been found to be useful in this condition.
 Fluid leakage around a faecal impaction is sometimes mistaken as diarrhoea. Loperamide is contraindicated in such scenario.
 Loperamide (2mg tablet) is recommended for the treatment of diarrhoea in the WHO

Guidelines for the clinical management of HIV infections in adults.
 Loperamide is included in the IAHPC List of Essential Medicines in Palliative Care (expert opinion) for the treatment of diarrhoea.

Evidence for management of this symptom
 A recent systematic review on loperamide for treatment of diarrhoea in palliative care patients identified that loperamide was superior compared to placebo and to acetorphan, though the comparison with octreotide was less conclusive
 Considering the low level of evidence from clinical trials, the recommendation for loperamide is based on expert opinion.

Adapted from Radbruch L et al. Essential medicines in palliative care - An application for the 19th WHO Expert committee on the selection and use of essential medicines. Kindle Edition, 135 pages. Published June 5th 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C

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